Minocycline prevents neurotoxicity induced by cerebrospinal fluid from patients with motor neurone disease

Tikka, Tiina; Vartiainen, Nina; Goldsteins, Gundars; Oja, Simo S.; Andersen, Peter M.; Marklund, Stefan L.; Koistinaho, Jari

doi:10.1093/brain/awf068

Cited by 127 publications

(84 citation statements)

References 75 publications

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“…In contrast to these findings, others have also demonstrated similar glutamate levels in CSF from patients with ALS and controls [83,84]. Interestingly, another study shows lower levels of glutamate in the CSF that fails to correlate to disease progression or decreased MN cell death [85]. However, measurements of CSF concentrations of glutamate in response to therapeutics remains to be explored and therefore further investigation is warranted.…”

Section: Metabolic Biomarkersmentioning

confidence: 91%

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Bowser

2017

Neurotherapeutics

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Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease with no effective treatment. Drug development has been hampered by the lack of biomarkers that aid in early diagnosis, demonstrate target engagement, monitor disease progression, and can serve as surrogate endpoints to assess the efficacy of treatments. Fluid-based biomarkers may potentially address these issues. An ideal biomarker should exhibit high specificity and sensitivity for distinguishing ALS from control (appropriate disease mimics and other neurologic diseases) populations and monitor disease progression within individual patients. Significant progress has been made using cerebrospinal fluid, serum, and plasma in the search for ALS biomarkers, with urine and saliva biomarkers still in earlier stages of development. A few of these biomarker candidates have demonstrated use in patient stratification, predicting disease course (fast vs slow progression) and severity, or have been used in preclinical and clinical applications. However, while ALS biomarker discovery has seen tremendous advancements in the last decade, validating biomarkers and moving them towards the clinic remains more elusive. In this review, we highlight biomarkers that are moving towards clinical utility and the challenges that remain in order to implement biomarkers at all stages of the ALS drug development process.

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Section: Metabolic Biomarkersmentioning

confidence: 91%

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Bowser

2017

Neurotherapeutics

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“…Minocycline has been shown to have a neuroprotective effect in animal models of other neurologic conditions such as multiple sclerosis (MS), 33,34 Parkinson disease, 11 Huntington disease, 35,36 amyotrophic lateral sclerosis (ALS), 36,37 and traumatic brain disease. 10,38 In some of these conditions, minocycline has had a therapeutic benefit in clinical trials.…”

Section: Statistical Methods For the Primary Analysis An Intention-mentioning

confidence: 99%

Minocycline treatment for HIV-associated cognitive impairment

et al. 2011

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Objective: We conducted a study of minocycline to assess its safety, tolerability, and efficacy for the treatment of HIV-associated cognitive impairment.Methods: HIV-1-infected individuals with progressive neurocognitive decline were enrolled in a double-blind, placebo-controlled study of minocycline. Participants were randomized to receive minocycline 100 mg or matching placebo orally every 12 hours. The primary efficacy measure was change in a neuropsychological test composite z score (NPZ-8) from baseline to week 24. Measures of safety included the frequency of adverse events and changes over time in laboratory tests. After 50% of participants completed the double-blind phase, an interim analysis of futility for the primary outcome measure was performed, and our Data and Safety Monitoring Board recommended early study termination.Results: A total of 107 HIV-1-infected individuals with cognitive impairment were enrolled. The minocycline group did not show improvement in the primary outcome measure (NPZ-8) (mean 24-week change ϭ 0.12) compared to placebo (mean 24-week change ϭ 0.17) (95% confidence interval ϭ [Ϫ0.26, 0.39], p ϭ 0.70). There were few severe adverse events or laboratory abnormalities in either treatment group.

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“…Similar findings were reported by Kriz et al (2002) and Van Den Bosch et al (2002), who showed that minocycline delayed the onset of motor neuron degeneration and muscle strength decline and increased the longevity of amyotrophic lateral sclerosis mice. Additional in vitro studies revealed that minocycline reduced the apoptosis of cultured neurons from patients with motor neuron diseases, including amyotrophic lateral sclerosis (Tikka et al, 2002). As is the case for Huntington's and Parkinson's diseases, the usefulness of minocycline in this neurological condition remains controversial, however.…”

Section: Effects Of Minocycline On Cns Pathologiesmentioning

confidence: 99%

Minocycline: far beyond an antibiotic

Garrido-Mesa

Zarzuelo

Gálvez

2013

British J Pharmacology

761

597

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Minocycline is a second‐generation, semi‐synthetic tetracycline that has been in therapeutic use for over 30 years because of its antibiotic properties against both gram‐positive and gram‐negative bacteria. It is mainly used in the treatment of acne vulgaris and some sexually transmitted diseases. Recently, it has been reported that tetracyclines can exert a variety of biological actions that are independent of their anti‐microbial activity, including anti‐inflammatory and anti‐apoptotic activities, and inhibition of proteolysis, angiogenesis and tumour metastasis. These findings specifically concern to minocycline as it has recently been found to have multiple non‐antibiotic biological effects that are beneficial in experimental models of various diseases with an inflammatory basis, including dermatitis, periodontitis, atherosclerosis and autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. Of note, minocycline has also emerged as the most effective tetracycline derivative at providing neuroprotection. This effect has been confirmed in experimental models of ischaemia, traumatic brain injury and neuropathic pain, and of several neurodegenerative conditions including Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Alzheimer's disease, multiple sclerosis and spinal cord injury. Moreover, other pre‐clinical studies have shown its ability to inhibit malignant cell growth and activation and replication of human immunodeficiency virus, and to prevent bone resorption. Considering the above‐mentioned findings, this review will cover the most important topics in the pharmacology of minocycline to date, supporting its evaluation as a new therapeutic approach for many of the diseases described herein.

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Minocycline prevents neurotoxicity induced by cerebrospinal fluid from patients with motor neurone disease

Cited by 127 publications

References 75 publications

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Minocycline treatment for HIV-associated cognitive impairment

Minocycline: far beyond an antibiotic

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